We propose to study two different aspects of the relationship between nutritional status and non-respiratory lung function. The first hypothesis is that availability of choline in the diet is rate limiting for lung synthesis of surfactant phospholipids and that lung may be uniquely sensitive to its deficiency. The second hypothesis is that dietary trace metals (mangenese and selenium) are required for the maintenance of lung anti-oxidant defenses and for the development of tolerance of hyperoxia. Through dietary manipulation, rats will be made deficient in choline, choline plus methionine, selenium or manganese. For project number one, we will evaluate the pool size of lung and granular pneumocyte phospholipids, lung pressure-volume curves, and lung lamellar body volume density. Using in vivo models, the isolated perfused lung, and isolated granular pneumocytes, we will evaluate rates of specific precursor incorporation and measure activities of key enzymes for the synthesis of disaturated phosphatidyl choline (DSPC). Special attention will be focused on possible induction of the ethanolamine methylation pathway for DSPC synthesis in the face of choline deficiency. Results will be compared with similar studies in liver since we postulate that lung phospholipid synthesis may be even more sensitive than liver to choline deprivation. For project number two, lungs and isolated granular pneumocytes from animals deficient in the specific trace metals (Mn, Se) will be evaluated for activities of key anti-oxidant enzymes including superoxide dismutases, glutathione peroxidase, and catalase and their response to hyperoxic exposure. Rats deficient in trace metals will be evaluated for their ability to develop tolerance in 80% oxygen and their survival in 1 ata O2. These studies will provide insights into control mechanisms for two basic lung metabolic functions and will in addition provide an important framework for defining clinical conditions when these specific deficiencies may adversely affect lung function.